WO2014021387A1 - ラテックス凝集阻害免疫法 - Google Patents

ラテックス凝集阻害免疫法 Download PDF

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WO2014021387A1
WO2014021387A1 PCT/JP2013/070775 JP2013070775W WO2014021387A1 WO 2014021387 A1 WO2014021387 A1 WO 2014021387A1 JP 2013070775 W JP2013070775 W JP 2013070775W WO 2014021387 A1 WO2014021387 A1 WO 2014021387A1
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polyoxyethylene
latex
absorbance
solution
group
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PCT/JP2013/070775
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English (en)
French (fr)
Japanese (ja)
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恵子 服部
壮一 北野
道子 川本
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積水メディカル株式会社
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Priority to US14/418,824 priority Critical patent/US10627393B2/en
Priority to EP13825736.5A priority patent/EP2881738B1/en
Priority to JP2014528199A priority patent/JP6334401B2/ja
Priority to CN201380050336.2A priority patent/CN104685359B/zh
Publication of WO2014021387A1 publication Critical patent/WO2014021387A1/ja

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54313—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals the carrier being characterised by its particulate form
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/5306—Improving reaction conditions, e.g. reduction of non-specific binding, promotion of specific binding
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L71/00—Compositions of polyethers obtained by reactions forming an ether link in the main chain; Compositions of derivatives of such polymers
    • C08L71/02—Polyalkylene oxides
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/543—Immunoassay; Biospecific binding assay; Materials therefor with an insoluble carrier for immobilising immunochemicals
    • G01N33/54393—Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
    • C08G2650/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
    • C08G2650/28—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule characterised by the polymer type
    • C08G2650/58—Ethylene oxide or propylene oxide copolymers, e.g. pluronics
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
    • C08L2203/00—Applications
    • C08L2203/02—Applications for biomedical use
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2400/00—Assays, e.g. immunoassays or enzyme assays, involving carbohydrates

Definitions

  • the present invention relates to a method for avoiding a non-specific reaction in a latex immunoagglutination measurement method caused by some component in a blood sample, and a reagent used for the avoidance method.
  • the latex immunoagglutination measurement method (hereinafter sometimes referred to as LTIA) is a method for measuring a test substance using latex particles on which an antigen or antibody is immobilized, and is widely used in the field of clinical examination.
  • LTIA a method for measuring an antigen as a test substance by LTIA
  • latex particles to which an antibody against the test substance is immobilized and an antigen as a test substance are reacted to form a sandwich-type immune complex
  • immune A method of measuring a test substance (antigen) from the degree of aggregation of the latex particles associated with the complex formation hereinafter sometimes referred to as sandwich LTIA
  • sandwich LTIA sandwich LTIA
  • the test substance) to inhibit the formation of immune complexes between the latex particles and the antibody, and the test substance (antigen) is determined based on the degree of inhibition of latex particle aggregation associated with the inhibition of immune complex formation. It can be roughly classified into the measurement methods (hereinafter
  • LTIA agglutination that should not occur in latex particles to which an antigen or antibody is immobilized by some component contained in the test sample, despite the absence of the test substance in the test sample such as serum, does not occur. Occasionally, it will occur or the aggregation that should occur does not occur. These are called non-specific reactions and are known to cause various measurement errors.
  • Patent Document 1 describes a method of adding an inorganic boron compound to a sample solution in combination with a buffer system as a method of removing non-specific turbidity (synonymous with non-specific aggregation) in sandwich LTIA.
  • this method is a method for eliminating the occurrence of aggregation that should not occur in the measurement method using latex particles to which antibodies are immobilized, and is a method that can cope with the fact that aggregation that should occur does not occur in aggregation inhibition LTIA. is not.
  • a buffer solution containing no blood component is measured as a test sample even though it is a blood sample that does not contain a test substance due to the influence of some component in the blood sample. In some cases, only an agglomeration degree lower than the agglomeration degree obtained at the time can be obtained.
  • the standard substance for concentration conversion of the test substance in the test sample hereinafter sometimes referred to as the standard substance for concentration conversion
  • the degree of aggregation does not match and deviates.
  • a method that can avoid a nonspecific reaction that aggregation that should occur does not occur in aggregation-inhibiting LTIA has not been established, and development of a new method has been required.
  • An object of the present invention is to provide a method capable of avoiding a nonspecific reaction that aggregation that should occur does not occur in aggregation-inhibiting LTIA.
  • POE-POP block copolymer polyoxyethylene polyoxypropylene block copolymer
  • POE alkyl ether oxyethylene alkyl ether
  • POE fatty acid ester polyoxyethylene fatty acid ester
  • polyvalent quaternary amine polymer compound polyvalent quaternary amine polymer compound
  • the present invention has the following configuration.
  • Latex in the presence of one or more compounds selected from the group consisting of polyoxyethylene-polyoxypropylene block copolymers, polyoxyethylene alkyl ethers, polyoxyethylene fatty acid esters, and polyvalent quaternary amine polymer compounds A method for avoiding a non-specific reaction in a latex agglutination inhibition method, comprising performing an agglutination inhibition measurement method.
  • the non-specific reaction is a non-specific reaction in which aggregation that should occur does not occur when a test substance is not present in the test sample.
  • R 1 O (C 2 H 4 O) n H (II) (Wherein R 1 is an alkyl group having 8 to 20 carbon atoms (the alkyl group may be either primary or secondary, and has at least one double bond in the alkyl group). And n represents an arbitrary integer of 7 to 40.)
  • ⁇ 5> The method according to ⁇ 1> or ⁇ 2>, wherein the polyoxyethylene fatty acid ester is represented by the formula (III).
  • R 2 COO (C 2 H 4 O) n R 3 (III) (Wherein R 2 represents an alkyl group having 16 to 18 carbon atoms (the alkyl group may have one or more double bonds), n represents an arbitrary integer of 170 to 180, R 3 represents a hydrogen atom or an R 2 COO group.)
  • ⁇ 6> The method according to ⁇ 1> or ⁇ 2>, wherein the polyvalent quaternary amine polymer compound is polybrene (CAS number: CB1327317).
  • a reagent for latex aggregation inhibition method comprising a polyoxyethylene-polyoxypropylene block copolymer, a polyoxyethylene alkyl ether, a polyoxyethylene fatty acid ester, and a polyvalent quaternary amine polymer compound
  • One or more selected compounds are contained in any one or more of the following (1) to (4): (1) Concentration conversion standard substance (2) Solution containing anti-test substance antibody (3) Solution containing latex particles with immobilized antigen (4) Solution for dissolving or diluting concentration conversion standard substance ⁇ 8>
  • the reagent according to ⁇ 7> which is used for measuring teicoplanin in a human blood sample.
  • ⁇ 9> One or more compounds selected from the group consisting of polyoxyethylene-polyoxypropylene block copolymers, polyoxyethylene alkyl ethers, polyoxyethylene fatty acid esters and polyvalent quaternary amine polymer compounds as active ingredients Non-specific reaction avoidance agent for latex aggregation inhibition method.
  • a curve ( ⁇ ) and a calibration curve ( ⁇ ) when human serum added with the test substance is diluted with human serum not added with the test substance It is a figure of the result of having examined the composition of the standard substance dilution liquid for concentration conversion containing the nonspecific reaction avoidance compound of this invention.
  • a calibration curve ( ⁇ ) when the standard substance for concentration conversion is diluted with the standard substance dilution liquid for concentration conversion of the present invention, and human serum to which the test substance is added are diluted with human serum to which the test substance is not added. This is a calibration curve ( ⁇ ).
  • Non-specific reaction avoidance compound examples include one or more compounds selected from the group consisting of POE-POP block copolymers, POE alkyl ethers, POE fatty acid esters, and polyvalent quaternary amine polymer compounds.
  • the polyoxyethylene polyoxypropylene block copolymer (POE-POP block copolymer) of the present invention has a structure represented by the following formula (I). [Chemical 1] HO (C 2 H 4 O) a - (C 3 H 6 O) b - (C 2 H 4 O) c H (I) (Wherein a, b and c represent arbitrary integers, a + c is determined to be ethylene oxide having an average polymerization degree of 4 to 200 units (hereinafter sometimes referred to as EO), and b is 5 (Determined to be propylene oxide having an average degree of polymerization of ⁇ 100 units (hereinafter sometimes referred to as PO))
  • Specific examples of commercially available products containing the POE-POP block copolymer used in the present invention include “F” among nonionic surfactants generally sold under the name of “Pluronic (registered trademark)”.
  • notation As components of the POE-POP block copolymer, and it is possible to confirm the identity and similarity between each notation, but even if it is a commercial product with the same name, the numerical value between each notation May not match exactly. These are specific to the polymerizable polymer and can be understood by those skilled in the art.
  • Pluronic F77 (1) Polyoxyethylene content 70%, polyoxypropylene molecular weight approximately 2306 (2) Number of EO-number of PO: (52x2) -35
  • Pluronic F87 (1) Polyoxyethylene content 70%, polyoxypropylene molecular weight approximately 2644 (2) EO number-PO number: (62x2) -39
  • Pluronic F88 (1) Polyoxyethylene content 80%, polyoxypropylene molecular weight approximately 2644 (2) EO number-PO number: (97x2) -39
  • Pluronic F68 (1) Polyoxyethylene content 80%, polyoxypropylene molecular weight approximately 1967 (2) Number of EO-Number of PO: (75x2) -30 Epan 485 (1) Polyoxyethylene content 85%, polyoxypropylene molecular weight approximately 1200 (2) Number of EO-number of PO: (80x2) -21 Epan 680 (1) Polyoxyethylene content 80%, polyoxypropylene molecular weight approximately
  • the polyoxyethylene alkyl ether (POE alkyl ether) of the present invention has a structure represented by the following formula (II). [Chemical 2] R 1 O (C 2 H 4 O) n H (II) (Wherein R 1 is an alkyl group having 8 to 20 carbon atoms (the alkyl group may be either primary or secondary, and has at least one double bond in the alkyl group). And n represents an arbitrary integer of 7 to 40.) Specific examples of commercial products containing the POE alkyl ether used in the present invention include “BT”, “BC” among nonionic surfactants generally sold under the name “NIKKOL (registered trademark)”. ”Or“ BO ”.
  • Nikkor BC40TX (3) Polyoxyethylene cetyl ether (4) R 1 : carbon number 16, n: 40
  • Nikkor BO10TX (3)
  • Polyoxyethylene oleyl (4) R 1 carbon number 18, n: 10
  • Nikkor BT-7 (3)
  • Nikkor BT-9 (3)
  • the polyoxyethylene fatty acid ester (POE fatty acid ester) of the present invention has a structure represented by the following formula (III).
  • R 2 COO (C 2 H 4 O) n R 3 (III) (Wherein R 2 represents an alkyl group having 16 to 18 carbon atoms (the alkyl group may have a double bond), n represents an arbitrary integer of 170 to 180, and R 3 represents Represents a hydrogen atom or R 2 COO group.)
  • Specific examples of commercially available products containing the POE fatty acid ester used in the present invention are enclosed in “DS” among nonionic surfactants generally sold under the name of “Neugen (registered trademark)”. Product can be mentioned. More specific examples of commercially available products are given together with the notations (5) and (6) as components that can be confirmed.
  • Neugen DS-601 (5) Polyoxyethylene distearate (6)
  • R 1 carbon number 17, n: 175
  • polyvalent quaternary amine polymer compound examples include polybrene (CAS number: CB1327317).
  • the non-specific reaction avoidance compound of the present invention dissolves a concentration-converting standard substance (so-called calibrator), a solution containing an anti-test substance antibody, a solution containing latex particles with immobilized antigen, and a concentration-converting standard substance. It can be used by adding to one or more reagents for performing aggregation-inhibiting LTIA, such as a solution for dilution. Among these, it is preferable to add to the standard substance for concentration conversion.
  • the preferred concentration of the nonspecific reaction avoiding compound is the concentration in the state in which the three components of the standard substance for concentration conversion, the anti-test substance antibody, and the latex particles on which the antigen is immobilized coexist in the reaction system (in the reaction system).
  • Final concentration of 0.003 to 0.078% (v / v, the same shall apply hereinafter), more preferably 0.006 to 0.034%, and particularly preferably 0.007 to 0.024%.
  • the non-specific reaction avoidance compound of the present invention is not limited to the effects of the present invention, and can guarantee the performance as a formulation.
  • Buffers, proteins, salts, preservatives and the like usually used in LTIA Can be used as a mixture.
  • Buffer solution for example, a buffer solution having a buffering action near neutral pH, preferably pH 6.5 to 7.8, more preferably pH 6.8 to 7.5 (phosphate buffer solution, Good buffer solution, glycine).
  • a buffer solution, a borate buffer solution, a wide-area buffer solution in which a plurality of buffer agents are combined, and the like are preferable.
  • the concentration of the buffering agent in these buffers is preferably 0.1 mM to 1 M, more preferably 1 mM to 800 mM, and particularly preferably 5 mM to 500 mM.
  • a buffer having an amine structure in the molecule for example, Tris
  • Components other than the nonspecific reaction-avoiding compound of the present invention can be selected by experimentation in consideration of the characteristics of each test substance.
  • protein Proteins include, but are not limited to, bovine serum albumin (BSA) and casein. These are used for the purpose of improving the storage stability of latex particles on which antibodies and antigens are immobilized, or for the purpose of aligning the reaction environment by approximating the concentration of protein components that a blood sample brings into the reaction system. .
  • BSA bovine serum albumin
  • casein casein
  • salts examples include, but are not limited to, sodium chloride and potassium chloride.
  • Preservatives include, but are not limited to, antibacterial agents such as ofloxacin and sodium azide.
  • a latex competition method in which the degree of aggregation of latex particles to which an antigen is immobilized is reduced according to the concentration of the test substance in the test sample.
  • the test substance can be measured by optically or electrochemically observing the degree of aggregation that has occurred. Examples of the optical observation method include a method of measuring scattered light intensity, absorbance, or transmitted light intensity with an optical instrument.
  • the test sample to be measured by the latex agglutination inhibition measurement method using the nonspecific reaction avoidance compound of the present invention is a blood sample such as serum or plasma.
  • the test substance (detection target) in the test sample include low molecular antigens such as peptide antigens and haptens.
  • peptide antibiotics such as teicoplanin, arbekacin, vancomycin, synthetic antibacterial agents such as ofloxacin
  • Test substances suitable for competitive immunoassay such as egg white and beans-derived allergens, can be mentioned. Of these, teicoplanin is preferred.
  • the antibody used in the present invention may be a polyclonal antibody or a monoclonal antibody.
  • a functional fragment of an antibody having antigen-antibody reaction activity can be used, and a general animal (mouse, goat, sheep, etc.) immunization process In addition to those obtained through the process, those obtained using genetic recombination techniques and chimeric antibodies can also be used.
  • functional fragments of antibodies include F (ab ′) 2 and Fab ′, which are fragments having antigen-antibody reaction activity.
  • Functional fragments of these antibodies can be produced by treating the antibody obtained as described above with a proteolytic enzyme (for example, pepsin or papain).
  • these antibodies may be immobilized on latex particles, or may not be immobilized.
  • Latex particles examples include polystyrene, styrene-styrene sulfonate copolymer, methacrylic acid polymer, acrylic acid polymer, acrylonitrile butadiene styrene copolymer, vinyl chloride-acrylic acid ester copolymer, Examples thereof include polyvinyl acetate acrylate.
  • the average particle size of the latex particles is appropriately selected from 0.1 ⁇ m to 0.4 ⁇ m in consideration of the concentration of the test substance in the test sample or the detection sensitivity of the measuring instrument.
  • a physical adsorption (hydrophobic bond) method or a chemical bond method may be appropriately selected according to the characteristics of the antigen to be immobilized. it can.
  • a physical adsorption (hydrophobic bond) method a polyhapten is formed and adsorbed.
  • a binding functional group such as a maleimide group is introduced into the antigen. By utilizing it, it can be bound and immobilized on a binding functional group on the latex particle surface.
  • the reagent for aggregation inhibition LTIA containing the nonspecific reaction avoidance compound of this invention can be provided with any one or more of the following forms normally used, it is not limited to this.
  • Standard substance for concentration conversion sometimes called by name such as calibrator
  • a solution containing an antibody against a test substance sometimes referred to as an antibody solution, first test solution, etc.
  • Latex particle solution with immobilized antigen sometimes called by the name of latex reagent, second reagent, etc.
  • a solution for dissolving or diluting the standard substance for concentration conversion (sometimes called by a name such as a calibrator dilution)
  • the buffer containing the non-specific reaction avoidance compound of the present invention may be provided under the names of a standard substance for concentration conversion (calibrator), a specimen dilution, and the like. Equivalent to. (2) When a non-specific reaction avoiding compound of the present invention is contained in a solution containing an antibody against a test substance or (3) a latex particle solution on which an antigen is immobilized, avoiding the non-specific reaction of the present invention It can be provided as a solution containing the compound. In the above (1) to (4), as long as they are used in a series when the aggregation inhibition LTIA is performed, each may be provided independently or may be provided in a lump such as a kit. Absent.
  • the composition when the PBS tablet is a 100 mL solution is as follows. 800 mg NaCl, 20 mg KCl, 115 mg sodium monohydrogen phosphate (anhydrous), potassium dihydrogen phosphate (anhydrous) (4) Anti-teicoplanin antibody solution (containing 2.8 mg / mL anti-teicoplanin sheep polyclonal antibody and 0.5% BSA, pH 7.0, hereinafter referred to as antibody solution) (5) Teicoplanin-sensitized latex reagent (pH 7.2 or less, referred to as latex reagent) 2. Method Teicoplanin was diluted to 0, 5, 10, 25, 50, and 100 ⁇ g / mL with a standard solution to prepare a calibrator.
  • base serum to which teicoplanin was added so as to be 110 ⁇ g / mL was prepared in 10 stages (0, 11, 22, 33, 44, 55, 66, 77, 88, 99) with base serum without teicoplanin or a standard substance dilution. , 110 ⁇ g / mL) to prepare simulated sample solution 1 and simulated sample solution 2 respectively.
  • simulated sample solution 1 or simulated sample solution 2 and 180 ⁇ L of anti-teicoplanin antibody solution were mixed and mixed at 37 ° C. for 5 minutes.
  • the dabs of the base serum itself are compared with the dabs of the calibrator (standard substance dilution solution itself) with a teicoplanin concentration of 0 ⁇ g / mL.
  • Example 1 Investigation of search for nonspecific reaction avoidance compound Reagent (1) Serum obtained from teicoplanin non-administered human (base serum) (2) Anti-teicoplanin antibody solution (antibody solution) (3) Teicoplanin sensitized latex reagent (latex reagent) For the above (1) to (3), the same ones as in Comparative Example 1 were used. (4) 10% BSA-2 ⁇ PBS (pH 7.0) One PBS tablet and 5 g of BSA were made up to 50 ml with water to make 10% BSA-2 ⁇ PBS. (5) The searched compounds are shown in Table 1. (A) Blocking N101 and N102 (both manufactured by NOF Corporation).
  • Epan 750 (POE-POP block copolymer, manufactured by Daiichi Kogyo Seiyaku Co., Ltd.) (1) Polyoxyethylene content 50%, polyoxypropylene molecular weight approximately 2000 (2) EO number-PO number: (23x2) -34
  • C Pluronic L34 (POE-POP block copolymer, manufactured by ADEKA) (1) Polyoxyethylene content 40%, polyoxypropylene molecular weight approximately 870 (2) Number of EO-Number of PO: (7x2) -15
  • D Pluronic F68 (POE-POP block copolymer, manufactured by ADEKA)
  • E) Neugen DS601 (POE fatty acid ester, manufactured by Daiichi Kogyo Seiyaku Co., Ltd.)
  • F Nikkor BC40TX (POE alkyl ether, manufactured by Nikko Chemicals)
  • G Nikkor BO-10
  • test solution 1 prepared by mixing 2.4 ⁇ L of base serum or 10% BSA-2 ⁇ PBS and the searched compound prepared to double the final concentration described in Table 1 at a volume ratio of 1: 1 (test solution 1) was mixed with 180 ⁇ L of the antibody solution and mixed at 37 ° C. for 5 minutes. Subsequently, 60 ⁇ L of latex test solution was mixed, and after 37 ° C., 1 minute (absorbance I), 1 minute 20 seconds (absorbance II), 3 minutes (absorbance III), 3 minutes 20 seconds (absorbance IV). Absorbance at 700 nm was measured for each.
  • Example 2 Examination of Effective Concentration Range of Nonspecific Reaction Avoidance Compound (Candidate) -1 The effective concentration range was examined for the nonspecific reaction avoidance compound candidates narrowed down from the results of Example 1.
  • Reagent (1) Serum obtained from teicoplanin non-administered human (base serum) (2) Anti-teicoplanin antibody solution (antibody solution) (3) Teicoplanin sensitized latex reagent (latex reagent) For the above (1) to (3), the same ones as in Comparative Example 1 were used. (4) 10% BSA-2 ⁇ PBS (pH 7.0) (5) Nonspecific reaction avoidance compound (candidate) It is shown in Table 2.
  • Example 3 Examination of concentration range of nonspecific reaction avoiding compound-2 1.
  • Reagent (1) Serum obtained from teicoplanin non-administered human (base serum) (2) Anti-teicoplanin antibody solution (antibody solution) (3) Teicoplanin sensitized latex reagent (latex reagent) In the above (1) to (3), the same as those in Comparative Examples 1 and 2 were used.
  • Nonspecific reaction avoiding compound (a) Pluronic F88 (B) Nikkor BT-9 2.
  • Method 2.4 ⁇ L of base serum as well as 10% BSA-2 ⁇ PBS and an additive compound prepared at a concentration twice the final concentration described in Table 3 (test solution 3) were mixed at a ratio of 1: 1 (test solution 3). It was mixed with the antibody solution and mixed at 37 ° C. for 5 minutes. Subsequently, 60 ⁇ L of latex test solution was mixed, and after 37 ° C., 1 minute (absorbance I), 1 minute 20 seconds (absorbance II), 3 minutes (absorbance III), 3 minutes 20 seconds (absorbance IV). Absorbance at 700 nm was measured for each. The difference between (average value of absorbance II and absorbance I) and (average value of absorbance IV and absorbance III) was determined and defined as dabs.
  • ⁇ BSA 5%, PB- 1.75 g sodium chloride, 0.7 g Pluronic F88, 5 g BSA, 2 mg ofloxacin were weighed and made up to 100 mL.
  • ⁇ BSA 10%, PB- 1.75 g sodium chloride, 0.7 g Pluronic F88, 10 g BSA, 2 mg ofloxacin were weighed and made up to 100 mL.
  • ⁇ BSA 0%, PB + One PBS tablet, 0.7 g of Pluronic F88, 2 mg of ofloxacin were weighed and made up to 100 mL.
  • Example 4 A standard curve when the standard substance for concentration conversion is diluted with a buffer containing the nonspecific reaction avoiding compound of the present invention and a standard curve when diluted with human serum not containing a test substance.
  • Teicoplanin was diluted to 0, 5, 10, 25, 50, and 100 ⁇ g / mL with a standard solution to prepare a calibrator.
  • base serum to which teicoplanin was added so as to be 110 ⁇ g / mL was classified into 10 levels (0, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 ⁇ g / mL) with base serum without teicoplanin.
  • 2.4 ⁇ L of the calibrator and simulated sample solution 3 and 180 ⁇ L of anti-teicoplanin antibody solution were mixed and mixed at 37 ° C. for 5 minutes.

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PCT/JP2013/070775 2012-07-31 2013-07-31 ラテックス凝集阻害免疫法 WO2014021387A1 (ja)

Priority Applications (4)

Application Number Priority Date Filing Date Title
US14/418,824 US10627393B2 (en) 2012-07-31 2013-07-31 Latex agglutination inhibition immunoassay
EP13825736.5A EP2881738B1 (en) 2012-07-31 2013-07-31 Latex agglutination inhibition immunoassay
JP2014528199A JP6334401B2 (ja) 2012-07-31 2013-07-31 ラテックス凝集阻害免疫法
CN201380050336.2A CN104685359B (zh) 2012-07-31 2013-07-31 胶乳凝集抑制免疫测定

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JP2012-170603 2012-07-31
JP2012170603 2012-07-31

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JP6736797B1 (ja) * 2018-11-09 2020-08-05 積水メディカル株式会社 自動分析装置での免疫測定における異常検出抑制方法、及び免疫測定試薬
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US20180238871A1 (en) * 2015-10-30 2018-08-23 Lsi Medience Corporation Reagent and method for measuring thrombin-antithrombin complex
WO2017090103A1 (ja) * 2015-11-25 2017-06-01 デンカ生研株式会社 免疫分析方法及び試薬キット
JP6736797B1 (ja) * 2018-11-09 2020-08-05 積水メディカル株式会社 自動分析装置での免疫測定における異常検出抑制方法、及び免疫測定試薬
JP7431711B2 (ja) 2020-09-30 2024-02-15 三洋化成工業株式会社 免疫測定方法及び免疫測定用キット

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EP2881738B1 (en) 2018-05-30
US20150212075A1 (en) 2015-07-30
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